1
Q
Immunity
A
Ability of an organism to recognize and defend itself against specific pathogens or antigens.
2
Q
Immunology
A
science that studies the structure and functioning of the immune system.
3
Q
Immune system
A
Made up of cells and molecules that make up the body’s defense system against disease-causing agents.
2 primary functions:
1. Recognition of, and defense against foreign substances.
2. Establishment of immunosurveillance.
4
Q
430 BC
A
Plague of Athens, persons who recovered only could nurse the sick.
5
Q
15th century
A
Arabs and Chinese, infecting individuals with materials from the pustules of smallpox patients, providing a mild form of disease and induced immunity.
6
Q
1718
A
Lady Mary Wortley Montagu performed variolation.
7
Q
1796
A
Birth of immunology
Edward Jenner improved variolation; observed milkmaid who contracted cowpox rarely contracted smallpox. Called the technique as vaccination.
8
Q
1979
A
Smallpox was eradicated.
50 years after, most European countries initiated compulsory vaccination program.
9
Q
Louis Pasteur
A
Formulated the germ theory of disease.
He was interested in preventing diseases caused by microorganisms.
Used vaccines to induce immunity.
Worked with the the bacteria that caused chicken cholera.
Discovered the first attenuated vaccine.
10
Q
Attenuation or change may occur through:
A
- Heat
- Aging
- Chemical means
Remains the basis for many of the immunizations that are used today.
11
Q
Rabies vaccine discovery by Pasteur
A
He recognized that the cns was affected.
Spinal cords left to dry for a few days were less infectious to laboratory animals than fresh spinal cord.
Boy got bitten by a dog got vaccinated a series of 12 injections beginning with material from the least infectious cords and progressing to the fresher, more infectious material.
12
Q
Other attenuated vaccines of Pasteur:
A
- Temperature attenuated Bacillus anthracis.
- Attenuated vaccines of today.
- Sabin Polio vaccine.
- Anthrax vaccine.
- Chicken cholera vaccine.
13
Q
Other Types of Vaccines used today:
A
- Killed vaccine
- Suspensions of toxoid
* Attenuated bacterial toxins
* Tetanus toxin
- Suspensions of killed bacteria or viruses
* Diptheria vaccine - Sub-unit vaccine
- Hepatitis B
* Hepatitis B surface antigen
- Meningitis- Neisseria meningitidis capsular antigen
- Pneumonia - Streptococcus pneumoniae capsular antigen
- Neisseria meningitidis capsular antigen
- Glycoconjugate vaccine
- Carbohydrate antigens are conjugated to proteins
- Haemophilus influenzae Type B (HiB) - Nucleic acid vaccine
- Naked antigen DNA ( Not yet available for human use)
- Used to immunize mice against malaria and influenzae
- Injected into muscle to:- induce sustained expression of the antigen
- Generate immune response
14
Q
The discovery of phagocytosis:
A
Discovered by Elie Metchnikoff.
Cells that eat cells.
Immunity to disease was based on the action of these scavenger cells.
15
Q
Birth of humoral immunity
A
Noncellular elements in the blood were responsible for protection from microorganisms.
16
Q
Cellular vs Humoral Immunity
A
Almoth Wright linked the two theories.
Observed that certain humoral, or circulating, factors called opsonins acted to coat bacteria so that they became more susceptible to ingestion by phagocytic cells.
Non-specific serum factors known as antibodies and nonspecific factors known as acute-phase reactants increase non-specifically in any infection.
17
Q
Functions of the Immune System
A
- Defense
-3rd line of defense is a specific defense mechanism
- resists invasion by microorganisms
- prevents reinfection
Sometimes defense can result to:
- Immunosuppression (hypofunction)
* Neutropenia (immunosuppression secondary to drugs)
* Immunosuppression due to development of AIDS after HIV infection
- Defense can result to hyperfunction
* Inappropriate and abnormal response to external antigens like allergens
> allergy - Homeostasis
- To maintain Homeostasis damaged cellular substances are digested and removed- Result: specific cell types remain uniform and unchanged
- Sometimes there is hyperfunction of homeostasis
- abnormal response where antibodies react agains normal tissues and cells - seen in autoimmune diseases
- Result: specific cell types remain uniform and unchanged
- Surveillance
- Mutations - continually arise in the body but are normally recognized as foreign cells and destroyed.
Hypofunction of surveillance
- inability of immune system to perceive and respond to mutated cells
18
Q
Properties of the Immune System
A
- Specificity (The immune system responds) - recognize only one epitope
- Recognition (The immune system remembers)
- Memory
- Immune system has unique ability to remember the antigen
When foreign antigen comes > series of cellular changes occurs > formation of specific antibody or sensitized lymphocyte that attaches to a specific antigen
- 1st time exposure to antigen - Primary immune response
- Subsequent exposure to the same antigen - Secondary immune response - Self-limitation (The immune system recognizes the enemy)
- distinguish difference between the body’s own proteins and foreign proteins
- failure - leads to tissue destruction - Self-regulation (The immune system regulates)
a. immune system - regulate its action
b. Self-regulation allows the immune system to monitor itself by:
* “turning on when antigen invades
* turning off when invader has been eradicated
c. Regulation prevents the destruction of healthy or host tissues.
d. Inability to regulate results to chronic inflammation and damage to host tissues
19
Q
4 R’s of the Immune Response:
A
- Responds
- Regulates
- Remembers
- Recognizes.
20
Q
Natural immunity
A
born with it; innate
- does not require prior exposure to antigen to function
- not specific
- has no memory
- maybe exogenous (skin); endogenous (acid pH); phagocytic (PMNs); natural killers (NK cells)
- considered non-adaptive or nonspecific and are the same for all pathogens or foreign substances to which one is exposed.
- no prior exposure is required, and the response does not change with subsequent exposures
- made up of the first and second line of defenses
- external defense system
- internal defense system
21
Q
Factors influencing natural immunity:
A
- Nutrition
- Age - number one factor
- Fatigue
- Stress
- Genetic determinants
22
Q
Nonspecific defense mechanisms
A
First line of defense: - Skin - Mucous membranes - Secretions of skin and mucous membranes Second line of defense - Phagocytic white blood cells - Antimicrobial proteins - The inflammatory response
23
Q
Specific defense mechanisms (immune system)
A
Third line of defense:
- Lymphocytes
- Antibodies
24
Q
External defense ( First line of defense)
A
Physical barrier ( epithelial cells, pH of skin surface, trapping of bacteria in mucus)
- Age determines immune system function
- Designed to keep microorganisms from entering the body
- If these are overcome, the internal defense must clear invaders ASAP
25
Internal defenses ( Second line of defense)
categorized into cellular mechanisms and humoral factors
- fluids secreted by cells and tissues (complement and interferon)
- Phagocytic: the process of macrophage or neutrophil engulfing bacteria
- Both of these systems work together to promote phagocytosis
- Inflammation: body processes such as: cellular movement, tissue repair, chemical release, elimination of foreign material
- inflammation brings cells and humoral factors to the area in need of healing
26
Barrier Defenses - First line of Defense
A. Phyiscal Barriers
1. Skin: First Line of Defense
- Primary organ of protection
- Lined with normal flora to make the skin pH acidic
- Has layers of lipid and fatty acids
- acts as a chemical barrier- controlling the entrance and exit of substances
- keratinized
- Thick/ tough
- Waterproof
- Very effective if unbroken
- Compacted
- Cemented
- Impregnated with insoluble keratin
- Constantly flaked/ desquamated
- Hair shaft is periodically extruded
- Sweat glands constantly flushed
- With normal flora
- With layers of lipid; fatty acids
- Site of chemical barriers - controlling the entrance and exit of substances
27
3 layers of the skin
1. Epidermis - outermost layer of the skin
- provides a waterproof barrier
- creates skin tone
- contain melanocytes
- special cells that give's skin color
- produces the pigment melanin
5 layers :
1. Stratum basale - deepest layer
2. Stratum spinosum - made of desmosomes to join adjacent cells together
3. Stratum granulosom - made of keratinocytes
4. Stratum lucidum - second later and varies in thickness depending on the frictional forces
5. Stratum corneum - made of dead skin cells
2. Dermis
- Found beneath the epidermis
- Contains tough connective tissue, hair follicles, and sweat glands
- with 2 layers
1. Papillary dermis - produces ridges (fingerprints)
2. Reticular dermis - coarse elastic fibers, irregular connective tissue made of collagen - responsible for stretch marks or striae
3. Hypodermis
- "deeper subcutaneous tissue"
- made of fat and connective tissue
- dermo-epithelial junction
- holds dermis and epidermis together
28
Functions of the skin
1. Regulates body temperature
2. Conserve body heat
3. During hard exercise, blood vessels narrow so that blood is able to circulate to the contracting muscles and increase perspiration
4. Protection
5. Sensation
6. Secretes sweat
29
Mucous membrane
```
not covered by skin
Lines respiratory tract, digestive tract, eyes
Thin, moist, permeable
Moistened through:
1. Blinking/lacrimation
2. Flow of saliva
3. acidic stomach
4. defecation
5. vomiting
```
30
Chemical barriers
Found in:
1. Mucus
2. Saliva
3. Sweat
4. Tears
31
Genetic barriers
exists in the negative sense
| - Protection is by lack of something rather than by its presence
32
The Second Line of Defense (Non-specific)
A. Acute phase reactants
- normal serum constituents that increase rapidly
- produced primarily by hepatocytes (liver parenchymal cells) to an increase in certain intercellular polypeptides called cytokines
- Cytokines produced: IL-1B, IL-6, and tumor necrosis factor-alpha (TNF-a)
1. C-Reactive Protein (CRP) -
2. Serum Amyloid A
3. Fibrinogen
4. Complement system proteins
5. Mannose- Binding Protein (MBP)
33
C-Reactive Protein (CRP)
increases rapidly following infection, surgery, or other trauma
- declines rapidly with cessation of the stimulus
- plasma half-life = 19 hours
- Pentraxins
- 118,000 daltons
- bind to small ribonuclear proteins; phospholipids; peptidoglycan; and other constituents of bacteria, fungi, and parasites
- nonspecific form of antibody molecule that is able to act as a defense against microorganisms or foreign cells until specific antibodies can be produced
34
Serum Amyloid A
major protein
- apolipoprotein synthesized in the liver
- molecular weight = 11,685 daltons
- 30 ug/ml
- thought to play a role in metabolism of cholesterol
- increase significantly more in bacterial infections than in viral infections
35
Fibrinogen
most abundant of the coagulation factors in plasma
- forms the fibrin clot
- 340,000 daltons
- increases the strength of a wound and stimulates endothelial cell adhesion and proliferation
- formation of a clot also creates a barrier that helps prevent the spread of microorganisms
36
Complement system proteins
- mediation of inflammation
- nine such proteins known as the classical cascade
- major functions of the complement system:
* Opsonization
* Chemotaxix
* lysis of cells
37
Mannose- Binding Protein (MBP)
trimer, acts as opsonin, calcium-dependent
| - widely distributed on mucosal surfaces throughout the body
38
Alpha1-Antitrypsin
major component of the alpha band when serum is electrophoresed
39
Elastase
enzyme that can degrade elastin and collagen
40
Monuclear Phagocyte System (MPS)
Composed of:
- Lymphatic Tissue
- Leukocytes
- Thymus gland
- Lymphocytes
- Chemical mediators
- Known before as Reticuloendothelial System (RES)
41
Two types of mononuclear phagocytic cells
1. Fixed macrophages
| 2. Free macrophages
42
Blood monocytes > migrate to various tissues > Mature to macrophages > Tissue macrophages scattered in connective tissues or clustered in organs:
```
Lungs (alveolar macrophages)
Liver ( Kupffer cells)
CNS (microglial cells)
splenic macrophages
- lymph node macrophages
- Tissues (Histiocytes)
- Kidneys (mesangial cells)
```
43
Pleuripotent hematopoeietic stem cell
Gives rise to WBCs, RBCs, and platelets
| - may either produce other stem cells and self-regenerate
44
How do hematopoeitic stem cells evolve?
1. Erythropoiesis
2. Lymphopoiesis
3. Granulopoiesis
45
Erythropoiesis
- sustained by multipotent stem cell
| - CFU-E is influenced by the hormone erythropoietin
46
Lymphopoiesis
- After maturation, it enters the peripheral blood
- it repopulates lymph nodes or lympathic organs
- Growth is conditioned by the thymus T cells and bone marrow for B cells
47
Granulopoiesis
Controlled by GM-CSF
| Share a common progenitor cell, CFU-GM
48
How was hematopoiesis studied?
In vitro BM cultures were performed
49
Why is the marrow the site for hematopoiesis?
Provieds a special environment for hematopoietic growth and development
- BM is extravascular
- single layer of endothelial cells separate the extravascular marrow compartment from intravascular compartment
50
Stem cell factor (SCF)
aka KIT-ligand, KL, or steel factor
- cytokine that binds to the c-KIT receptor (CD117)
- a transmembrane protein and a soluble protein
51
Functions of the SCF
plays a role in the hematopoiesis during embryonic development
52
Ligand
molecule that binds to a receptor
53
SCF evolution
gene encoding is on chromosome 12q22-12q24 in humans
54
White Blood Cells
all contain nuclei and organellese unlike RBC
55
Leukocytosis
infection or inflammation
56
Neutrophilia
bacterial infection
57
Eosinophilia
allergic reaction
58
Lymphocytosis
Ag/AB reactions
59
Leukopenia
low white cell count
60
Functions of the WBC
fight invasion by non-self via phagocytosis or through specific responses through antibody production
Help defend the body against invasion by pathogens, and they remove toxins, wastes, and abnormal cells
61
Special Characteristics of the WBC
Increase during stress
6000 to 9000 WBCs
Most are in the connevtive tissue proper or in organs of the lympathic system
62
Characteristics of circulating WBCs
amoeboid movement
- migrate out of the bloodstream by squeezing thru endothelial cells (process called diapedesis)
- attracted to specific chemical stimuli (positive chemotaxis)
- prdxn and maturation of granulocytes, 14 days
Distribution:
- Marrow Reserve
- Circulating Pool - in the blood
- Marginating Pool - along the endothelium, spleen
63
Neutrophils
9-15 um in diameter
- diurnal variation (Afternoon)
- known as Polymorphonuclear (PMNs)
- 50-70% of WBCs in PB
- 40-75% of total WBC (50-70% of storage)
Nucleus
- Coarse and clumped chromatin
- Segmented Nucleus 2-5 lobes
- Lobes are joint only by threadlike filaments
Cytoplasm
- Pink to rose-violet specific (secondary) granules
- Primary and secretory granules
Function: phagocytic
- attacking and digesting bacteria
- cytoplasm contain bactericidal compounds
- first WBC to arrive at an injury site (w/n 6 hours from injury)
- Lifespan: 24-48 hrs
64
2 types of Neutrophils
1. Band (immature) - horseshoe-shape
- especially during inflammation, the bone marrow releases immature neutrophils
2. Segmented (mature)
65
Eosinophils
9-15 um in diameter
- 1-5% of WBCs in PB
* 2-5% of total WBC
- Diurnal variation due to ACTH influence
Nucleus
- Coarse and clumped
- bi-lobed
- joint only by threadlike filaments
Cytoplasm
- reddish-orange
- primary granules, lysosomal granules, lipid bodies and storage vesicles
- at sites of parasitic infection, or at allergic sites
- main method of attack is the exocytosis of toxic compounds
- Function weakly phagocytic, suppresses inflammation and decreases granulocyte migration
- increase in a parasitic infection
- sensitive to allergens and increase in allergic reaction
66
Basophils
10-16 um diameter
- 1-5% of WBC in PB
- Scarcest in circulation at 0.2 to 0.5 % of total WBC
Nucleus
- Coarse and clumped
- unsegmented or bilobed
- covered by large granules
Cytoplasm
- Dark purple to black purple
- large water-soluble specific granules
Function: inflammatory mediator release
- 8-10 um in diameter
- share same morphology with Mast Cells
- migrate to injury sites and discharge the contents of their granules (motile)
* histamine
* enhances the local inflammation and attracts other WBCs
* granules contain serotonin
67
Lymphocytes
with very complex kinetics
- relative count 20%-40%
- 20%-30%
Absolute count - 0.96 - 4.4 x 103/mm3
Categorized as specialized cells:
- Not in the end-stage in the PB
- Recirculation tissue-blood-tissue-blood
- capable of extensive genetic recombination
- mature and selected outside the BM
1. T cells: defend against foreign cells and tissues and coordinate the immune response
2. B cells: produce and distribute antibodies that attack foreign materials
- B cells were first demonstrated in special lymphatic glands of birds called Bursa of Fabricious
3. Natural Killer Cells - no antigen-specific receptor
68
Lymphocyte development
- controlled by environmental and hormonal stimuli separate from the granulocytes and monocytes
- circulate all throughout
- stimulated by specific hormone stimuli (CFU-L)
69
2 Primary Lymphoid Organs
```
Bone Marrow (B cells)
Thymus (T cells)
```
70
Plasma cell
The end of a B cell maturation
| Produce antibodies
71
2 groups of Lymphocytes
T and B lymphocytes
- Antigen-activated (macrophages and dendritic cells)
- release macrophage-activating cytokines
72
Secondary Lymphoid Tissues
T cells - Perifollicular and paracortical regions of lymph nodes
- Medullary cords of lymph nodes
B cells - Follicular and medullary regions of lymph nodes
- red pulp of spleen
- Follicular regions of GALT
- medullary cords of lymph nodes
73
T- cell Classes:
1. T helper cells
a. TH1 Cells
b. TH2 Cells
c. TH17 Cells - extracellular bacteria
d. Treg Cells - maintain self-tolerance
2. . T cytotoxic cells
74
Natural Killer Cells
Part of innate immunity
- Attacks without prior sensitization
- Targets Tumor cells and virus-laden cells
- Derived from both BM and Thymus
- "large granular lymphocytes" - contain peroxidase negative granules
75
Markers of NK cells:
CD2 - adhesion/signal transduction molecule
CD8 - (variable) MHC class I receptor
CD16 (FcyII) - low affinity receptor for IgG (ab-dependet cell-mediated cytotoxicity)
CD56 - adhesion molecule
76
Macrophages/Monocytes
2%-10% circulating leukocytes
Absolute Count - 0.096 -1.1 x103/mm3
- Promonocytes - mitotically active stage
- Attracted secondarily to acute inflamed sites
- cell in chronic inflammation
Distribution:
No storage pool
Splenic pool
Circulating pool
Marginating pool (3.5x the circulating pool)
77
Tissue pool (Macrophage)
most abundant
- Relatively long-lived and retains ability to multiply
- process foreign molecule and presents them to lymphcoytes
- serves as antigen-processing cells and APC's (Antigen-Presenting Cell) together with dendritic cells
- activated by the presence of antigen
- secrete cytokines that cause increase in body temperature
78
Functions of Macrophages
1. Acts as professional phagocytes in innate immunity
2. Participates in adaptive immunity as antigen-presenting cells
3. Maintenance Functions for homeostasis
a. Clean-up of debris and dead cells
b. Destruction of senescent red cells and iron recycling
4. Synthetic Functions (it can secrete)
a. Complements
b. Coagulation factors
c. Prostaglandins
d. Leukotrienes
e. Growth factors
f. Transferrin
79
Tissue Pool of Macrophages:
1. Liver - Kupffer cells
2. Lungs - alveolar macrophages
3. Brain - Microglial
4. Skin - Langerhans cells
5. Spleen - Splenic macrophages
6. Intestines - intestinal macrophages
7. Peritoneum - peritoneal macrophages
8. Bone - osteoclasts
9. Synovium - type A cell
10. Kidneys - renal macrophages
11. Reproductive organ macrophages
12. Lymph nodes - dendritic cells
80
Monocyte Maturation Markers:
```
Monocyte Precursor Receptors
1. M-CSF R
2. Lysozyme Receptor
Mature Cell Receptors
* CD11b/CD18
* Macrophage Receptors
> CD68/macrosialin - lipoprotein met
> Sialoadhesin - cell-cell or cell-ECM interactions
CD14 - most important functional marker
- receptor for LPS
```
81
The Inflammatory Response
non-specific defense
- in-flame - to set fire (red, hot, pain)
Inflammation is a property of the 2nd line of defense
- serves to bring defense and healing mechanisms to the site of injury
82
Inflammation
A complex response to sublethal injury to a tissue
Sequential reaction to cell injury
It is physiologic, protective response
83
Phases of Inflammatory Response
1. Vascular
2. Cellular
3. Formation of Exudates
4. Healing
84
Chemical Mediators of the vascular response:
```
First mediator - Histamine
2nd Mediator - Bradykinin
Prostaglandins
Other inflammatory mediators
- Plasma proteases - protein activated under complement system
- Leukotrienes
- Mast Cells
- Oxygen Free Radicals - mediators
- Complement system
```
85
Histamine
lower allergen contained in our body
a vasoamine that causes:
-dilation of local blood vessels
- Contraction of smooth muscles
86
Bradykinin
Plasma protein formed when injury releases clotting factors (Factor Xii converts to Factor XIIa)
- leads to vascular permeability
- vasodilation
- smooth muscle contraction
87
Prostaglandins
```
Induce production of platelets
derived from arachidonic acid
- vasodilation
- pain
- fever
- platelet aggregation to help in clotting
```
88
Plasma proteases
protein activated under complement system
89
Leukotrienes
formed from arachidonic acid
- important mediator in bronchial asthma and immediate hypersensitivity reaction
- may cause vasodilation and increased capillary permeability
90
Complement system
primary mediator of the humoral immune system response
- helps body produce inflammation and helps localize infectious agents
- enhances phagocytosis
- enhances chemotaxis
- increase blood vessel permeability
- cause cell lysis
91
Cellular Response
Migration
Diapedesis
Chemotaxis
Directional migration of WBC along a concentration
Ensure accumulation of neutrophils and monocytes at the focus of injury
Immunology for Medical Technology
flashcards
Decks in class (1)
# Cards
